Studies on the relation between the biological function and the dynamic properties of rat liver plasma and microsomal membranes

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To elucidate the relation between the cellular function and the dynamic properties of biomembranes, we studied the membrane fluidity and nitroxide reduction activity of rat liver microsomes with spin-label technique.1. Four spin-labeled stearic acids were used as both probes for membrane fluidity and substrates for nitroxide reduction by NADPH cytochrome P-450 reductase - cytochrome P-450 system. Active center of nitroxide reduction of microsomes was found to locate around 7-12 carbon position of stearic acid in membranes. The nitroxide reduction was induced by the administration of phenobarbital but not by 3-methylcholanthrene. However, the membrane fluidity of liver microsomes increased by the administration of phenobarbital, polychlorinated biphenyls or 3-methylcholanthrene.2. Oral administration of C <Cl_4> , CH <Cl_3> , CH <Br_3> and CH <Br_2> Cl changed membrane structure and nitroxide reduction activity of rat liver microsomes. ESR spectrum of methyl ester of spin-labeled steari … More c acid in microsomes showed the presence of non-bilayer and bilayer phases in membranes. The transfer rate of the spin probes between two phases was changed by the oral administration of these compounds. Nitroxide reduction rate also decreased by the treatment. Among these compounds, C <Cl_4> gave the most influence on the membrane fluidity and nitroxide reduction.3. In vitro treatment of C <Cl_4> and CH <Br_3> to rat liver microsomes caused lipid peroxidation of microsomal membranes in addition to decrease of cytochrome P-450 contents, arylesterase and demethylase activity when NADPH generating system was added, but not in the absence of the system. These compounds increased the membrane fluidity of liver microsomes, while the metabolites of the compounds decreased. Nitroxide reduction activity of microsomes also decreased by the compounds themselve, but much decrease was observed in the presence of NADPH generating system.4. Long-term administration of phenobarbital to rat caused significant decrease of the activity in drug metabolizing enzymes. Less